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| Status |
Public on Sep 20, 2014 |
| Title |
Tsc1 promotes the differentiation of memory CD8+ T cells via orchestrating the transcriptional and metabolic programs |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Memory CD8+ T cells are an essential component of protective immunity. Signaling via mechanistic target of rapamycin (mTOR) has been implicated in the regulation of the differentiation of effector and memory T cells. However, little is understood about the mechanisms that control mTOR activity, or the effector pathways regulated by mTOR, in this process. We describe here that tuberous sclerosis 1 (Tsc1), a regulator of mTOR signaling, plays a crucial role in promoting the differentiation and function of memory CD8+ T cells in response to Listeria monocytogenes infection. Mice with specific deletion of Tsc1 in antigen-experienced CD8+ T cells evoked normal effector responses, but were markedly impaired in the generation of memory T cells and their recall responses to antigen re-exposure in a cell-intrinsic manner. Tsc1 deficiency suppressed the generation of memory-precursor effector cells (MPECs) while promoting short-lived effector cell (SLEC) differentiation. Functional genomic analysis indicated that Tsc1 coordinated gene expression programs underlying immune function, transcriptional regulation and cell metabolism. Furthermore, Tsc1 deletion led to excessive mTORC1 activity and dysregulated cellular metabolism including glycolytic and oxidative metabolism. These findings establish a Tsc1-mediated checkpoint in linking immune signaling and cell metabolism to orchestrate memory CD8+ T cell development and function.
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| Overall design |
We used microarrays to explore the gene expression profiles differentially expressed in OVA-specific CD8+ T-cells from wild-type (WT; Tsc1-fl/fl and cre-negative) and Tsc1-/- (Tsc1-fl/fl and Granzyme B-cre-positive) mice
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| Contributor(s) |
Shrestha S, Yang K, Neale G, Chi H |
| Citation(s) |
25271321 |
| |
| Submission date |
Sep 19, 2014 |
| Last update date |
Aug 06, 2018 |
| Contact name |
Geoffrey Neale |
| E-mail(s) |
geoffrey.neale@stjude.org
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| Organization name |
St Jude Childrens Research Hospital
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| Department |
Hartwell Center
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| Street address |
262 Danny Thomas Place
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (1) |
| GPL11180 |
[HT_MG-430_PM] Affymetrix HT MG-430 PM Array Plate |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA261548 |
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